According to the United Network for Organ Sharing (UNOS), there are more than 92,000 individuals in the United States on the organ transplant waiting list as of June 2006. The number of people of the waiting list continues to increase every year. However, the number of available deceased organs has remained about the same. The result is a shortage of organs and a longer time on the wait list. UNOS has reported that approximately 6,500 transplant candidates died in 2005 while awaiting an organ transplant. Each day approximately 17 people die while waiting for a transplant of a vital organ, such as a heart, liver, kidney, pancreas, lung or bone marrow. A primary cause of the long wait times is the lack of available organs for transplant.
Today, the primary source of transplant organs is from cadaveric donors, also referred to as heart beating donors (HBD). Heart beating donors are donors that have been clinically declared brain dead and who are being maintained on life support. Transplants from non-beating heart donors, also referred to as DCD donors, are procured after cessation of cardiopulmonary function in the donor, and can occur in a controlled setting, after a planned withdrawal of life support, or in an uncontrolled situation with the onset of sudden cardiac arrest.
Traditionally, DCD organs have not been widely accepted for transplantation because of ethical and medical concerns. The major ethical issues involving DCD organs focused on whether the procurement of DCD organs violated the “dead-donor rule” in that the retrieval of organs for transplantation does not cause the death of a donor. With the acceptance of cardiopulmonary criterion for determining the death of the prospective organ donor, the ethical issues associated with DCD organs have largely been resolved. Based on a cardiopulmonary criterion, DCD donor death occurs when respiration and circulation have ceased and cardiopulmonary function will not resume spontaneously.
Medical concerns for the use of DCD organs have generally focused on the viability of organs recovered from DCD donors. Because DCD organs are not harvested until after the cessation of cardiopulmonary function, these organs are commonly associated with injury that results from warm ischemia. Warm ischemia is characterized by a decrease or complete stop of blood flow to one or several organs. It is generally believed that organs that have been exposed to warm ischemia for periods approaching 30 minutes are not suitable for transplantation. For instance, studies have shown that increased warm ischemia time in livers results in increases in cellular injury, ATP deprivation, and microvascular thrombosis, which can result in impairments in hepatic function upon reperfusion. Injury in DCD organs can also result from reperfusion, which refers to the restoration of blood flow to the organs. Studies have shown that ischemia followed by reperfusion induces apoptosis and inflammation that can cause tissue damage and organ dysfunction, which is called ischemia-reperfusion (I/R) injury or reperfusion injury. Ischemia-reperfusion injury accompanying organ transplantations can result in dysfunction of the transplanted organ and in some cases, death of the patient.
Cold preservation has been shown to help reduce injuries associated with ischemia and improve the viability of transplant organs. The main purpose of cold preservation is to suppress metabolic and proteolytic activities during storage so that the organ may remain viable for transplantation over a longer period of time. Generally, there are two primary forms of cold preservation. Simple cold storage is the most common and involves flushing the blood out of the organ and infusing it with a cold preservation solution. The second method is hypothermic machine perfusion (HMP) and involves continuous perfusion of the organ with a perfusate maintained at a temperature between 4° C. and 8° C. Conventionally, perfusion is done at low pressure and usually with the pulsatile flow of about 0.6 to 10 ml/min/g of tissue.
Several preservation solutions aiming at minimizing tissue damage in the organ transplants during hypothermal storage have been developed. One such solution, which is commonly referred to as the University of Wisconsin (UW) solution, has been shown to be effective for reducing reperfusion injury in kidneys obtained from BHD donors. The UW solutions are described in greater detail in U.S. Pat. Nos. 4,798,824 and 4,879,283. While the UW solution and some other preservation solutions, such as the Euro-Collins solution (Squifflet J. P. et al., Transplant. Proc. 13:693-696, 1981), have been effective in extending the cold preservation time of organs intended for transplantation, tissue injury during cold storage and particularly during reperfusion still occurs. Additionally, such solutions have not adequately addressed injuries that have occurred in DCD organs prior to perfusion of the preservation solution as a result of warm ischemia. As a result, DCD organs, such as the liver and pancreas, may still not be suitable for transplantation.
Thus, there exists a need for a solution and a method for improving the viability of organs recovered from DCD donors.